Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues

Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues
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DOI:
10.1158/1078-0432.ccr-06-1820
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发表时间:
2007-02-01
影响因子:
11.5
通讯作者:
Kunz, Manfred
Kunz, Manfred
中科院分区:
医学1区
文献类型:
--
作者:
Jaeger, Jochen;Koczan, Dirk;Kunz, Manfred

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目的:为了更好地了解恶性黑色素瘤进展和转移的分子机制,对原发黑色素瘤和黑色素瘤转移瘤的基因表达谱进行了研究。实验设计:激光捕获显微切割黑色素瘤细胞后,用寡核苷酸芯片分析19例原发黑色素瘤和22例黑色素瘤转移瘤中肿瘤细胞特异性基因的表达。统计分析采用随机排列分析和支持向量机。结果:共鉴定出308个在原发黑色素瘤和转移性黑色素瘤中差异表达显著的基因(假发现率为085%)。进一步分析表明,原发黑色素瘤的亚型和细小肿瘤(2.0 mm Breslow厚度)具有特征性的基因表达模式。结论:这项针对恶性黑色素瘤的大规模基因表达研究确定了与转移、黑色素瘤亚型和肿瘤厚度相关的分子特征。这些发现不仅为黑色素瘤进展的发病机制提供了更深入的见解,还可能指导未来创新治疗的研究。
Purpose: To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases.Experimental Design: Tumor cell-specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting.Results: Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate 085% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (2.0 mm Breslow thickness).Conclusions: Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.